Inter-laboratory comparison of routine autoantibody detection methods for autoimmune neuropathies and myasthenia gravis.

Serological tests are important to detect autoantibodies (autoAbs) in patients with autoimmune neuropathies (AN) and myasthenia gravis (MG) as they are biomarkers for diagnosis, stratification, treatment selection, and monitoring. However, tests to detect autoAbs frequently lack proper standardization and results differ across diagnostic laboratories. We compared results for tests routinely performed in Spanish diagnostic laboratories to detect AN and MG autoAbs. In the Spanish Society of Immunology Autoimmunity Group national workshop, serum samples from 13 patients with AN or MG were tested for anti-ganglioside, anti-myelin-associated glycoprotein (MAG), anti-nicotinic acetylcholine receptor (AChR), and anti-muscle-specific kinase (MuSK) autoAbs using reference methods and were distributed for analysis to 27 participating laboratories using their routine methods. Overserved were inter-laboratory variability and worryingly low sensitivity, especially for anti-ganglioside immunoglobulin G and anti-MAG autoAb detection. This pilot study reflects autoAbs detection state of the art in AN and MG testing in leading diagnostic laboratories in Spain, highlighting the need for standardization prior to clinical use.

Diagnostic Value of Krebs von den Lungen (KL-6) for Interstitial Lung Disease: A European Prospective Cohort.

INTRODUCTION: Krebs von den Lungen 6 (KL-6) is a mucin-1 glycoprotein produced by type II pneumocytes. High levels of KL-6 in blood may be found in patients with lung fibrosis. In Asia this biomarker is used for diagnosis and prognosis in interstitial lung diseases (ILD). There is a lack of information regarding KL-6 cut-off point for diagnosis and prognosis in European population. The aim of this study was to establish the cut-off point for serum KL-6 associated with the presence of ILD in the Spanish population. METHODS: Prospective study including subjects who underwent chest HRCT, PFTs and autoimmune blood analysis. Two groups were created: non-ILD subjects and ILD patients. Serum KL-6 concentrations were measured using a Lumipulse KL-6 reagent assay and the optimal cut-off value was evaluated by a ROC analysis. Data on demographics and smoking history was also collected. RESULTS: One hundred seventy-nine patients were included, 102 with ILD. Median serum KL-6 values overall were 762U/mL, 1080 (±787)U/mL for the ILD group vs 340 (±152)U/mL for the non-ILD group (p<0.0001). The main radiological pattern was NSIP (43%). ROC analysis showed greater specificity (86%) and sensitivity (82%) for KL-6 465U/mL for detecting ILD patients. The multivariate logistic regression model pointed to the male sex, higher KL-6 values, lower FVC and low DLCO values as independent factors associated with ILD. CONCLUSION: Serum KL-6 values greater than 465U/mL have excellent sensitivity and specificity for detecting ILD in our Spanish cohort. Multicentre studies are needed to validate our results.

[Exploring Needs, Motivations, and Limitations Towards Healthy Eating and Digital Resources: A Qualitative Study in a Mexican Primary Education Setting]. / Exploración de necesidades, motivaciones y limitaciones en relación con la alimentación saludable y recursos digitales: un estudio cualitativo en un entorno de educación primaria en México.

OBJECTIVE: To explore the needs, motivations, and limitations related to healthy eating and digital materials, as well as to identify patterns for their design as a strategy aimed at Mexican families. DESIGN: A qualitative observational study of the phenomenon through focus group sessions. LOCATION: A public primary education center in the city of Querétaro, Mexico. PARTICIPANTS: Children aged 9 to 11 years and parents, mothers, or caregivers with children in primary education. METHOD: Twelve sessions were conducted with three groups of students and two sessions with parents, mothers, or caregivers using an interview guide. Various digital materials, developed based on social cognitive theory, were presented during the sessions. The sessions were recorded with the participants' or their guardians' prior consent and transcribed for analysis. Coding was performed for key points of analysis, and information saturation was confirmed. RESULTS: Students expressed motivation towards digital material that promotes play and experimentation, especially within the family context. The main perceived barrier was the caregivers' resistance to change. Parents expressed motivation and a need for explanatory material on diseases, with economic and time-related barriers. CONCLUSIONS: Digital material based on social cognitive theory, designed to improve nutrition, can be an effective strategy in nutritional education if it considers the circumstances of the target population. It is advisable to include affective and behavioral elements to achieve meaningful learning within households.

Validación de una escala enfermera para evaluar las actitudes del profesorado en la atención diabética / Validation of a nursing scale for assessing teachers' attitudes to diabetes care

Objetivo: Validar el Inventario de Actitudes Negativas del Profesorado hacia la Atención del Alumnado con Diabetes Mellitus tipo 1 (INAPAD) y estudiar su fiabilidad mediante los coeficientes Alfa de Cronbach y Omega de McDonald. Material y método: Este estudio describe el proceso de diseño y validación de la escala enfermera INAPAD en una muestra de 382 docentes en las etapas de Educación Infantil, Educación Primaria, Educación Secundaria Obligatoria, Bachillerato y Formación Profesional en una provincia española. El INAPAD pretende valorar diversas dimensiones actitudinales sobre la atención educativa al alumnado con Diabetes Mellitus tipo 1, incidiendo tanto en el perfil docente y profesional del profesorado, como en las características y necesidades específicas de este alumnado. Por su parte, la validez de constructo se ha evaluado mediante análisis factoriales exploratorios por componentes principales y rotación varimax. Resultados y Conclusión: Los resultados obtenidos informan de la viabilidad del INAPAD para ser utilizado como un instrumento útil para el diagnóstico del prejuicio o predisposición del profesorado hacia la atención del alumnado con DM tipo 1 y, por ende, para predecir el éxito de las medidas psicopedagógicas y los cuidados del niño y adolescente con diabetes. (AU)

Objective: To validate the Inventory of Teachers' Negative Attitudes towards the Care of Students with Diabetes Mellitus type 1 (INAPAD) and to study its reliability using Cronbach's Alpha and McDonald's Omega coefficients. Enfermería GlobalNº 74 Abril 2024Página 195Methods: This study describes the design and validation process of the INAPAD nursing scale in a sample of 382 teachers in the stages of Early Childhood Education, Primary Education, Compulsory Secondary Education, Baccalaureate and Vocational Training in a Spanish province. In order to validate the INAPAD, its reliability has been studied using Cronbach's Alpha and McDonald's Omega Coefficients. Hence, the construct validity has been evaluated through exploratory factor analysis by principal components and varimax rotation. Results and conclusion: The findings obtained inform the viability of the INAPAD to be used as an effective instrument for the diagnosis of prejudice or predisposition of educators towards the care of learners with type 1 DM and for the prediction of the success of psycho-pedagogical measures and of the care for children and adolescents with diabetes. (AU)

Prognostic significance of lymphocytic foci composition in minor salivary gland biopsies for severe disease flare and severity in Sjögren's syndrome: a 3-year follow-up cohort study.

Introduction: This was an ambispective cohort study evaluating the prognostic significance of lymphocytic foci and its lymphoid composition in minor salivary gland biopsy (MSGB) for short-term disease flare and severity in Sjögren's syndrome (SS). Methods: The inclusion criteria comprised individuals meeting the ACR/EULAR 2016 criteria who underwent MSGB with an infiltration of more than 50 lymphocytes and received clinical diagnosis between September 2017 and December 2018. Patients with inadequate biopsy samples were excluded. The number of lymphocytic foci and their lymphoid composition in MSGB were assessed using immunofluorescence staining. Major organ damage and improvements in the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) were measured. Statistical analyses, including Cox and linear regressions, were conducted. Results: A total of 78 patients with at least one lymphocytic focus were included in the study. The presence of higher T-cell counts in lymphocytic foci in MSGB was associated with severe disease flare, and a logarithmic transformation of T-cell count indicated increased risk (HR 1.96, 95% CI 0.91-4.21). Improvements in the ESSDAI were associated with higher total lymphocyte count and T- and B-cell numbers in the lymphoid composition of the lymphocytic foci. Seropositive patients exhibited higher T CD4+ cell numbers. Correlation analysis showed negative associations between age and lymphocytic foci and the T-cell count. Positive correlations were observed between antinuclear antibody (ANA) titers and total lymphocyte numbers. Discussion: Patients with a higher number of T cells in the lymphocytic infiltrates of lymphocytic foci may have a two-fold risk of severe disease flare. The number of B cells and T CD4+ cells in the lymphocytic infiltrates of lymphocytic foci showed a weak but positive relation with the ESSDAI improvement during follow-up. Age and seropositivity appeared to influence the lymphoid composition of the lymphocytic foci.

Fossil Collection at the Zoology Museum of the University of Concepción: enhancing understanding of Chile's past biodiversity.

Background: The digital inventory of paleontological material stored in Chilean museums is highly relevant as it increases accessibility to information, both locally and over long distances, while reducing wear and tear on specimens caused by physical manipulation. The Fossil Collection database of the Museum of Zoology of the University of Concepción (UCC_MZUC_FOS) includes 144 records, with the main representatives being marine invertebrates of the Bivalvia, Echinoidea and Gastropoda classes. Notable species include Encopecalderensis, Hemiasterwayensis, Zygochlamyspatagonica and Retrotapesexalbidus, most of which come from important Chilean fossil sites. Material was collected between 1970 and 2017, with a large portion of it being donated and identified by Professor Emeritus Hugo I. Moyano and Dr. Alberto Larraín. Although the specimens contained in the resource offer basic collecting information, they substantially contribute to sharing knowledge on the fossils kept in the museums throughout the country, while providing data on their distribution. New information: This resource corresponds to the first publication of data on faunal fossils from a museum collection in Chile on the Global Biodiversity Information Facility (GBIF) platform, thereby enhancing the understanding and documentation of Chile's paleontological heritage and its national biodiversity.

Membrane Proteome-Wide Screening of Autoantibodies in CIDP Using Human Cell Microarray Technology.

BACKGROUND AND OBJECTIVES: Autoantibody discovery in complex autoimmune diseases is challenging. Diverse successful antigen identification strategies are available, but, so far, have often been unsuccessful, especially in the discovery of protein antigens in which conformational and post-translational modification are critical. Our study assesses the utility of a human membrane and secreted protein microarray technology to detect autoantibodies in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). METHODS: A cell microarray consisting of human embryonic kidney-293 cells expressing >5,000 human proteins was used. First, a validation step was performed with 4 serum samples from patients with autoimmune nodopathy (AN) to assess the ability of this technology to detect circulating known autoantibodies. The ability of the cell microarray technology to discover novel IgG autoantibodies was assessed incubating the array with 8 CIDP serum samples. Identified autoantibodies were subsequently validated using cell-based assays (CBAs), ELISA, and/or tissue immunohistochemistry and analyzed in a cohort of CIDP and AN (n = 96) and control (n = 100) samples. RESULTS: Serum anti-contactin-1 and anti-neurofascin-155 were detected by the human cell microarray technology. Nine potentially relevant antigens were found in patients with CIDP without other detectable antibodies; confirmation was possible in six of them: ephrin type-A receptor 7 (EPHA7); potassium-transporting ATPase alpha chain 1 and subunit beta (ATP4A/4B); leukemia-inhibitory factor (LIF); and interferon lambda 1, 2, and 3 (IFNL1, IFNL2, IFNL3). Anti-ATP4A/4B and anti-EPHA7 antibodies were detected in patients and controls and considered unrelated to CIDP. Both anti-LIF and anti-IFNL antibodies were found in the same 2 patients and were not detected in any control. Both patients showed the same staining pattern against myelinating fibers of peripheral nerve tissue and of myelinating neuron-Schwann cell cocultures. Clinically relevant correlations could not be established for anti-LIF and anti-IFNL3 antibodies. DISCUSSION: Our work demonstrates the utility of human cell microarray technology to detect known and discover unknown autoantibodies in human serum samples. Despite potential CIDP-associated autoantibodies (anti-LIF and anti-IFNL3) being identified, their clinical and pathogenic relevance needs to be elucidated in bigger cohorts.

Sex differences on constitutive long non-coding RNA expression: Modulatory effect of estradiol and testosterone in muscle cells.

INTRODUCTION: Despite the growing awareness of sexual dimorphism between males and females under pathological and physiological conditions, sex bias in biomedical research in animal models and patients is still present nowadays. The main objective of this work was to investigate sex differences in constitutive long non-coding RNA expression in spinal cord and skeletal muscle from wild-type mice. MATERIALS AND METHODS: To assess the influence of gender on long non-coding RNAs, we extracted RNA from tissues of male and female mice and analyzed the expression on nine long non-coding RNAs, selected for being among the most commonly studied or exerting an important role in muscle, at 50, 60, and 120 days of age. RESULTS AND DISCUSSION: We observed age- and tissue-dependent significant sex differences, being more prominent in skeletal muscle. We also studied the effect of sex steroid hormones on long non-coding RNA expression in vitro, noticing a modulation of long non-coding RNA levels upon estradiol and dihydrotestosterone treatment in muscle. CONCLUSIONS: Taken together, results obtained evidenced sex differences on constitutive long non-coding RNA expression and suggested an influence of steroid hormones complementary to other possible factors. These findings emphasize the importance of including both sexes in experimental design to minimize any potential sex bias.

Relationship between Nutrition and Development of the Jaws in Children: A Pilot Study.

Craniofacial growth and development have been shown to be influenced by various environmental factors that impact child development. This study aims to analyze the different patterns of feeding during early childhood, starting from birth, and assess the variability of nutrition during the first stage of childhood, along with the habits developed, to study their impact on jaw development. The study was conducted on a sample of twenty-five patients aged 3 to 5, following approval from the ethics committee of the Catholic University of Valencia. Informed consent was obtained from the fathers, mothers, and/or legal guardians, who were administered surveys on habits and diet. Cephalometric measurements within the parameters of ideal occlusion were subsequently taken. While previous studies examined this subject, the findings are challenging to evaluate. However, this study identified significant associations (p = 0.001) between clinical measurements and children's eating habits. The growth and development of the craniofacial cavity are influenced by multiple factors, including a child's diet and habits. Nonetheless, further research is required to determine whether diet can be considered a determining factor in proper jaw growth.

Gastroschisis prevalence patterns in 27 surveillance programs from 24 countries, International Clearinghouse for Birth Defects Surveillance and Research, 1980-2017.

BACKGROUND: Gastroschisis is a serious birth defect with midgut prolapse into the amniotic cavity. The objectives of this study were to evaluate the prevalence and time trends of gastroschisis among programs in the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR), focusing on regional variations and maternal age changes in the population. METHODS: We analyzed data on births from 1980 to 2017 from 27 ICBDSR member programs, representing 24 countries and three regions (Europe+ (includes Iran) , Latin America, North America). Cases were identified using diagnostic codes (i.e., 756.7, 756.71, or Q79.3). We excluded cases of amniotic band syndrome, limb-body wall defect, and ruptured omphalocele. Programs provided annual counts for gastroschisis cases (live births, stillbirths, and legally permitted pregnancy terminations for fetal anomalies) and source population (live births, stillbirths), by maternal age. RESULTS: Overall, gastroschisis occurred in 1 of every 3268 births (3.06 per 10,000 births; 95% confidence intervals [CI]: 3.01, 3.11), with marked regional variation. European+ prevalence was 1.49 (95%CI: 1.44, 1.55), Latin American 3.80 (95%CI: 3.69, 3.92) and North American 4.32 (95%CI: 4.22, 4.42). A statistically significant increasing time trend was observed among six European+ , four Latin American, and four North American programs. Women <20 years of age had the highest prevalence in all programs except the Slovak Republic. CONCLUSIONS: Gastroschisis prevalence increased over time in 61% of participating programs, and the highest increase in prevalence was observed among the youngest women. Additional inquiry will help to assess the impact of the changing maternal age proportions in the birth population on gastroschisis prevalence.

New Insights into Endogenous Retrovirus-K Transcripts in Amyotrophic Lateral Sclerosis.

Retroviral reverse transcriptase activity and the increased expression of human endogenous retroviruses (HERVs) are associated with amyotrophic lateral sclerosis (ALS). We were interested in confirming HERVK overexpression in the ALS brain, its use as an accessory diagnostic marker for ALS, and its potential interplay with neuroinflammation. Using qPCR to analyze HERVK expression in peripheral blood mononuclear cells (PBMCs) and in postmortem brain samples from ALS patients, no significant differences were observed between patients and control subjects. By contrast, we report alterations in the expression patterns of specific HERVK copies, especially in the brainstem. Out of 27 HERVK copies sampled, the relative expression of 17 loci was >1.2-fold changed in samples from ALS patients. In particular, the relative expression of two HERVK copies (Chr3-3 and Chr3-5) was significantly different in brainstem samples from ALS patients compared with controls. Further qPCR analysis of inflammation markers in brain samples revealed a significant increase in NLRP3 levels, while TNFA, IL6, and GZMB showed slight decreases. We cannot confirm global HERVK overexpression in ALS, but we can report the ALS-specific overexpression of selected HERVK copies in the ALS brain. Our data are compatible with the requirement for better patient stratification and support the potential importance of particular HERVK copies in ALS.

Evaluation of the implementation of a community health worker-led COVID-19 contact tracing intervention in Chiapas, Mexico, from March 2020 to December 2021.

BACKGROUND: Mexico is one of the countries with the greatest excess death due to COVID-19. Chiapas, the poorest state in the country, has been particularly affected. Faced with an exacerbated shortage of health professionals, medical supplies, and infrastructure to respond to the pandemic, the non-governmental organization Compañeros En Salud (CES) implemented a COVID-19 infection prevention and control program to limit the impact of the pandemic in the region. We evaluated CES's implementation of a community health worker (CHW)-led contact tracing intervention in eight rural communities in Chiapas. METHODS: Our retrospective observational study used operational data collected during the contract tracing intervention from March 2020 to December 2021. We evaluated three outcomes: contact tracing coverage, defined as the proportion of named contacts that were located by CHWs, successful completion of contact tracing, and incidence of suspected COVID-19 among contacts. We described how these outcomes changed over time as the intervention evolved. In addition, we assessed associations between these three main outcomes and demographic characteristics of contacts and intervention period (pre vs. post March 2021) using univariate and multivariate logistic regression. RESULTS: From a roster of 2,177 named contacts, 1,187 (54.5%) received at least one home visit by a CHW and 560 (25.7%) had successful completion of contact tracing according to intervention guidelines. Of 560 contacts with complete contact tracing, 93 (16.6%) became suspected COVID-19 cases. We observed significant associations between sex and coverage (p = 0.006), sex and complete contact tracing (p = 0.049), community of residence and both coverage and complete contact tracing (p < 0.001), and intervention period and both coverage and complete contact tracing (p < 0.001). CONCLUSIONS: Our analysis highlights the promises and the challenges of implementing CHW-led COVID-19 contact tracing programs. To optimize implementation, we recommend using digital tools for data collection with a human-centered design, conducting regular data quality assessments, providing CHWs with sufficient technical knowledge of the data collection system, supervising CHWs to ensure contact tracing guidelines are followed, involving communities in the design and implementation of the intervention, and addressing community member needs and concerns surrounding stigmatization arising from lack of privacy.

Role of maraviroc and/or rapamycin in the liver of IL10 KO mice with frailty syndrome.

Cellular senescence and low-grade inflammation favor the acceleration of aging. The liver is an essential metabolic organ because changes related to its function are related to age-related diseases. The objective of this study was to evaluate the effects of maraviroc (MVC) and/or rapamycin (RAPA) on liver tissue in an experimental model of frailty syndrome in mice, since MVC and RAPA are two molecules able to decrease CCR5 expression, which is overexpressed in patients with frailty. Methods: Eighty male homozygous IL10KO mice were randomly assigned to one of 4 groups (n = 20): i) IL10KO group; ii) MVC group, iii) RAPA group, and iv) MVC-RAPA group. Liver samples were analyzed. Gene expression quantification and western blotting were also performed. The proinflammatory cytokines IL-6 and IL-18 were decreased in MVC and MVC/RAPA groups, IL-12 was decreased in RAPA and MVC/RAPA groups and TNF-α was decreased in all therapeutic groups. P21 was decreased in RAPA and MVC/RAPA groups, Galactosidase beta-1, was also significantly reduced in all therapeutic groups, as were NF-kB1, NF-kB2 and STAT3. In all groups, mTOR and CCL5 were significantly reduced. CCR5 expression was decreased in the MVC and MVC/RAPA groups. Conclusion: MVC and RAPA may protect against some factors involved in liver aging. More studies will be necessary to verify their clinical applications.

Validation of the Health Protective Sexual Communication Scale Among Young Adults in the United Kingdom and Spain.

Background and Purpose: The transmission of sexual infections is increasing globally. The research aims to validate the Health Protective Sexual Communication Scale (HPSC) in English and Spanish. Methods: The study survey was administered to 1,223 university students from Spain (658) and the United Kingdom (565) during the academic year 2020-2021. Results: Cronbach's alpha values were .80 (Spain) and .86 (United Kingdom). The scale's Exploratory and Confirmatory Factor Analysis displays a one-dimensional structure of eight items in both countries. Conclusions: The HPSC has excellent reliability and validity. Psychometric findings support the use of the HPSC as a screening tool to measure sexual risk in youth.

Analysis of Plasma-Derived Exosomal MicroRNAs as Potential Biomarkers for Canine Idiopathic Epilepsy.

Epilepsy is one of the most prevalent complex neurological diseases in both the canine and human species, with the idiopathic form as its most common diagnosis. MicroRNAs (miRNAs) are small, noncoding RNA molecules that play a role in gene regulation processes and appear to be a promising biological target for convulsion control. These molecules have been reported as constituents of the internal content of exosomes, which are small extracellular vesicles released by cells. In this study, exosome samples were isolated from the plasma of 23 dogs, including 9 dogs with epilepsy responsive to treatment, 6 dogs with drug-resistant epilepsy, and 8 control dogs. Plasma exosomes were then characterized by electron transmission microscopy, nanoparticle tracking analysis, and dot blotting. Afterwards, the microRNA-enriched RNA content of exosomes was isolated, and miRNA quantification was performed by quantitative real-time PCR. Seven circulating miRNAs that have been previously described in the literature as potential diagnostic or prognostic biomarkers for epilepsy were evaluated. We observed significant differences in miR-16 (p < 0.001), miR-93-5p (p < 0.001), miR-142 (p < 0.001), miR-574 (p < 0.01), and miR-27 (p < 0.05) levels in dogs with refractory epilepsy compared to the control group. In drug-sensitive epileptic dogs, miR-142 (p < 0.01) showed significant differences compared to healthy dogs. Moreover, distinct levels of miR-16 (p < 0.05), miR-93-5p (p < 0.01), miR-132 (p < 0.05), and miR-574 (p < 0.05) were also found between drug-sensitive and drug-resistant epileptic dogs. Our results present plasma-circulating exosomes as an advantageous source of epileptic biomarkers, highlighting the potential of miRNAs as prognostic and diagnostic biomarkers of canine idiopathic epilepsy.

Optoacoustic Cooling of Traveling Hypersound Waves.

We experimentally demonstrate optoacoustic cooling via stimulated Brillouin-Mandelstam scattering in a 50 cm long tapered photonic crystal fiber. For a 7.38 GHz acoustic mode, a cooling rate of 219 K from room temperature has been achieved. As anti-Stokes and Stokes Brillouin processes naturally break the symmetry of phonon cooling and heating, resolved sideband schemes are not necessary. The experiments pave the way to explore the classical to quantum transition for macroscopic objects and could enable new quantum technologies in terms of storage and repeater schemes.

Cryptic splicing of stathmin-2 and UNC13A mRNAs is a pathological hallmark of TDP-43-associated Alzheimer's disease.

Nuclear clearance and cytoplasmic accumulations of the RNA-binding protein TDP-43 are pathological hallmarks in almost all patients with amyotrophic lateral sclerosis (ALS) and up to 50% of patients with frontotemporal dementia (FTD) and Alzheimer's disease. In Alzheimer's disease, TDP-43 pathology is predominantly observed in the limbic system and correlates with cognitive decline and reduced hippocampal volume. Disruption of nuclear TDP-43 function leads to abnormal RNA splicing and incorporation of erroneous cryptic exons in numerous transcripts including Stathmin-2 (STMN2, also known as SCG10) and UNC13A, recently reported in tissues from patients with ALS and FTD. Here, we identify both STMN2 and UNC13A cryptic exons in Alzheimer's disease patients, that correlate with TDP-43 pathology burden, but not with amyloid-ß or tau deposits. We also demonstrate that processing of the STMN2 pre-mRNA is more sensitive to TDP-43 loss of function than UNC13A. In addition, full-length RNAs encoding STMN2 and UNC13A are suppressed in large RNA-seq datasets generated from Alzheimer's disease post-mortem brain tissue. Collectively, these results open exciting new avenues to use STMN2 and UNC13A as potential therapeutic targets in a broad range of neurodegenerative conditions with TDP-43 proteinopathy including Alzheimer's disease.